Evidence suggests that insulin delivery to skeletal muscle interstitium is the rate-limiting step in insulin-stimulated muscle glucose uptake and that this process is impaired by insulin resistance. In this review we examine the basis for the hypothesis that insulin acts on the vasculature at three discrete steps to enhance its own delivery to muscle: (1) relaxation of resistance vessels to increase total blood flow; (2) relaxation of pre-capillary arterioles to increase the microvascular exchange surface perfused within skeletal muscle (microvascular recruitment); and (3) the trans-endothelial transport (TET) of insulin. Insulin can relax resistance vessels and increase blood flow to skeletal muscle. However, there is controversy as to whether this occurs at physiological concentrations of, and exposure times to, insulin. The microvasculature is recruited more quickly and at lower insulin concentrations than are needed to increase total blood flow, a finding consistent with a physiological role for insulin in muscle insulin delivery. Microvascular recruitment is impaired by obesity, diabetes and nitric oxide synthase inhibitors. Insulin TET is a third potential site for regulating insulin delivery. This is underscored by the consistent finding that steady-state insulin concentrations in plasma are approximately twice those in muscle interstitium. Recent in vivo and in vitro findings suggest that insulin traverses the vascular endothelium via a trans-cellular, receptor-mediated pathway, and emerging data indicate that insulin acts on the endothelium to facilitate its own TET. Thus, muscle insulin delivery, which is rate-limiting for its metabolic action, is itself regulated by insulin at multiple steps. These findings highlight the need to further understand the role of the vascular actions of insulin in metabolic regulation.

Purpose The study was designed to determine the incidence of postoperative agitation following general anesthesia in 2,000 adult patients and to examine the associated risk factors. Methods The study enrolled 2,000 adults who were scheduled for surgery under general anesthesia in a single institution during December 2007 to December 2008. The following risk factors were examined: age, gender, ASA physical status, type of surgery, anesthesia technique (inhalational or intravenous), administration of neostigmine or doxapram, adequate postoperative analgesia, pain, presence of a tracheal tube, and presence of a urinary catheter. Results Agitation occurred in 426 patients (21.3%). It was more common in males (28.1%) than in females (16.1%) (P = 0.017) and more prevalent after inhalational (27.8%) than total intravenous (7.5%) anesthesia (P = 0.001). Agitation was more common after oral cavity and otolaryngological surgery than after other types of surgery. Multivariate analysis showed that use of doxapram (odds ratio [OR] = 9.2; 95% confidence interval [CI] = 6.2 -15.4; P = 0.002) and pain (OR = 8.2; 95% CI = 4.5 -16.9; P \ 0.001) were the most important risk factors associated with emergence agitation. Other causes were the presence of a tracheal tube and/or a urinary catheter. Adequate postoperative analgesia was associated with less agitation (OR = 0.4; 95% CI = 0.1 -0.4; P = 0.006). Conclusion Doxapram administration, pain, and presence of a tracheal tube and/or a urinary catheter appear to be the most important causes of postoperative agitation. To avoid this complication, it is suggested, whenever possible, to use intravenous anesthesia, to remove endotracheal tubes and urinary catheters as early as possible, and to provide adequate postoperative analgesia. RésuméObjectif Cette e´tude a e´te´conçue afin de de´terminer l'incidence d'agitation postope´ratoire apre`s une anesthe´sie ge´ne´rale chez 2000 patients adultes et d'examiner les facteurs de risque associe´s. Méthode L'e´tude a recrute´2000 adultes devant subir une chirurgie sous anesthe´sie ge´ne´rale dans une seule institution entre de´cembre 2007 et de´cembre 2008. Les facteurs de risque suivants ont e´te´examine´s: l'aˆge, le sexe, le statut physique ASA, le type de chirurgie, la technique anesthe´sique (par inhalation ou intraveineuse), l'administration de ne´ostigmine ou de doxapram, une analge´sie postope´ratoire adapte´e, la douleur, la pre´sence d'une sonde endotrache´ale et la pre´sence d'un cathe´ter urinaire. Résultats Au total, 426 patients ont montre´des signes d'agitation (21,3 %). Elle e´tait plus courante chez les hommes (28,1 %) que chez les femmes (16,1 %) (P = 0,017) et plus pre´valente apre`s une anesthe´sie par inhalation (27,8 %) qu'apre`s une anesthe´sie re´alise´e exclusivement par intraveineuse (7,5 %) (P = 0,001). L'agitation e´tait plus fre´quente apre`s une chirurgie otorhinolaryngologique ou de la cavite´orale qu'apre`s d'autres types de chirurgie. Une analyse multivarie´e a montre´que l'utilisation de doxapram (rappo...

Glucagon-like peptide 1 (GLP-1) increases tissue glucose uptake and causes vasodilation independent of insulin. We examined the effect of GLP-1 on muscle microvasculature and glucose uptake. After confirming that GLP-1 potently stimulates nitric oxide (NO) synthase (NOS) phosphorylation in endothelial cells, overnight-fasted adult male rats received continuous GLP-1 infusion (30 pmol/kg/min) for 2 h plus or minus NOS inhibition. Muscle microvascular blood volume (MBV), microvascular blood flow velocity (MFV), and microvascular blood flow (MBF) were determined. Additional rats received GLP-1 or saline for 30 min and muscle insulin clearance/uptake was determined. GLP-1 infusion acutely increased muscle MBV (P < 0.04) within 30 min without altering MFV or femoral blood flow. This effect persisted throughout the 120-min infusion period, leading to a greater than twofold increase in muscle MBF (P < 0.02). These changes were paralleled with increases in plasma NO levels, muscle interstitial oxygen saturation, hind leg glucose extraction, and muscle insulin clearance/uptake. NOS inhibition blocked GLP-1–mediated increases in muscle MBV, glucose disposal, NO production, and muscle insulin clearance/uptake. In conclusion, GLP-1 acutely recruits microvasculature and increases basal glucose uptake in muscle via a NO-dependent mechanism. Thus, GLP-1 may afford potential to improve muscle insulin action by expanding microvascular endothelial surface area.

There have been an increasing number of reports implicating Gammaproteobacteria as often carrying genes of drug resistance from colonized sink traps to vulnerable hospitalized patients. However, the mechanism of transmission from the wastewater of the sink P-trap to patients remains poorly understood. Herein we report the use of a designated hand-washing sink lab gallery to model dispersion of green fluorescent protein (GFP)-expressing Escherichia coli from sink wastewater to the surrounding environment. We found no dispersion of GFP-expressing E. coli directly from the P-trap to the sink basin or surrounding countertop with coincident water flow from a faucet. However, when the GFP-expressing E. coli cells were allowed to mature in the P-trap under conditions similar to those in a hospital environment, a GFP-expressing E. coli-containing putative biofilm extended upward over 7 days to reach the strainer. This subsequently resulted in droplet dispersion to the surrounding areas (<30 in.) during faucet operation. We also demonstrated that P-trap colonization could occur by retrograde transmission along a common pipe. We postulate that the organisms mobilize up to the strainer from the P-trap, resulting in droplet dispersion rather than dispersion directly from the P-trap. This work helps to further define the mode of transmission of bacteria from a P-trap reservoir to a vulnerable hospitalized patient.IMPORTANCE Many recent reports demonstrate that sink drain pipes become colonized with highly consequential multidrug-resistant bacteria, which then results in hospital-acquired infections. However, the mechanism of dispersal of bacteria from the sink to patients has not been fully elucidated. Through establishment of a unique sink gallery, this work found that a staged mode of transmission involving biofilm growth from the lower pipe to the sink strainer and subsequent splatter to the bowl and surrounding area occurs rather than splatter directly from the water in the lower pipe. We have also demonstrated that bacterial transmission can occur via connections in wastewater plumbing to neighboring sinks. This work helps to more clearly define the mechanism and risk of transmission from a wastewater source to hospitalized patients in a world with increasingly antibiotic-resistant bacteria that can thrive in wastewater environments and cause infections in vulnerable patients.

Pancreatic neuroendocrine tumors (PNETs), a group of endocrine tumors arising in the pancreas, are among the most common neuroendocrine tumors. The genetic causes of familial and sporadic PNETs are somewhat understood, but their molecular pathogenesis remains unknown. Most PNETs are indolent but have malignant potential. The biological behavior of an individual PNET is unpredictable; higher tumor grade, lymph node and liver metastasis, and larger tumor size generally indicate a less favorable prognosis. Endocrine testing, imaging, and histological evidence are necessary to accurately diagnose PNETs. A 4-pronged aggressive treatment approach consisting of surgery, locoregional therapy, systemic therapy, and complication control has become popular in academic centers around the world. The optimal application of the multiple systemic therapeutic modalities is under development; efficacy, safety, availability, and cost should be considered when treating a specific patient. The clinical presentation, diagnosis, and treatment of specific types of PNETs and familial PNET syndromes, including the novel Mahvash disease, are summarized.